The career goal of this applicant is to provide a mechanistic rationale for making exercise regimens more effective at preventing chronic diseases. Coronary heart disease is the leading cause of death in the United States. Aerobic exercise is prescribed as a first-line of defense to decrease the risk of developing of atherosclerosis. Exercise training reduces plasma triglyceride concentration and increases [HDL-C]. Research suggests that a primary reason for improved blood lipids with exercise training is the increased muscle lipoprotein lipase expression. A long- term research goal of the applicant is to identify the exercise signals that upregulate LPL gene expression. The studies proposed will describe the time course of the increase in LPL mRNA during changes in rat muscle contractile activity. The proposed studies will identify an LPL 3' untranslated sequence that has a loss of RNA-protein interaction during increased contractile activity in vivo. Experiments will then determine if the LPL sequence decreases mRNA stability in cell culture experiments. Finally, the function of this LPL sequence as a regulatory element for gene expression in vivo will be determined by direct plasmid DNA injections into rat skeletal muscle.